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Review
. 2021 Sep 30:8:659388.
doi: 10.3389/fmolb.2021.659388. eCollection 2021.

tRNA Metabolism and Lung Cancer: Beyond Translation

Meng Bian  1 , Shiqiong Huang  2 , Dongsheng Yu  1 , Zheng Zhou  1
Affiliations
Review

tRNA Metabolism and Lung Cancer: Beyond Translation

Meng Bian et al. Front Mol Biosci. .

Abstract

Lung cancer, one of the most malignant tumors, has extremely high morbidity and mortality, posing a serious threat to global health. It is an urgent need to fully understand the pathogenesis of lung cancer and provide new ideas for its treatment. Interestingly, accumulating evidence has identified that transfer RNAs (tRNAs) and tRNA metabolism-associated enzymes not only participate in the protein translation but also play an important role in the occurrence and development of lung cancer. In this review, we summarize the different aspects of tRNA metabolism in lung cancer, such as tRNA transcription and mutation, tRNA molecules and derivatives, tRNA-modifying enzymes, and aminoacyl-tRNA synthetases (ARSs), aiming at a better understanding of the pathogenesis of lung cancer and providing new therapeutic strategies for it.

Keywords: lung cancer; pathogenesis; tRNA aminoacylation; tRNA derivatives; tRNA modifications; therapeutics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
tRNA-associated metabolism and lung cancer. tRNA, transfer RNA; TERT, telomerase reverse transcriptase; hTRM9L, tRNA methyltransferase 9-like; TRIT1, tRNA isopentenyltransferase 1; QTRT1, tRNA-ribosyltransferase 1; METTL1, methyltransferase-like 1; ARSs, aminoacyl-tRNA synthetases; AIMPs, ARS-interacting multifunctional proteins; IARS2, isoleucyl-tRNA synthetase 2; LRS, leucyl-tRNA synthetase; TyrRS, tyrosine-tRNA synthetase; NARS, asparaginyl-tRNA synthetase; MRS, methionyl-tRNA synthetase; and AIMP2-DX2, AIMP2 lacking exon 2.
FIGURE 2
FIGURE 2
Dysregulation of ARSs and AIMPs in lung cancer. IARS2 regulates lung cancer cell proliferation by activating the AKT/mTOR pathway. AIMP2 interacts with Smurf2 to downregulate c-Myc and sustains TGF-β signaling, thereby inhibiting tumorigenesis. Moreover, AIMP2-DX2 reduces the proapoptotic activity of AIMP2 by competitive binding to p53, which induces lung tumorigenesis. ARSs, aminoacyl-tRNA synthetases; AIMPs, ARS-interacting multifunctional proteins; IARS2, isoleucyl-tRNA synthetase 2; Smurf2, Smad ubiquitination regulatory factors 2; TGF-β, transforming growth factor-β; AIMP2-DX2, AIMP2 lacking exon 2.
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